Reconsidering the Diagnosis and Severity of Adrenal Insufficiency: A Cross-Sectional Study in Actual Clinical Practice

<h2>Abstract</h2><h3>Context</h3> Adrenal insufficiency (AI) is characterized by glucocorticoid deficiency, with symptoms such as fatigue and hypoglycemia. Since AI presents with various severities in actual clinical settings, its evaluation using endocrine stress tests also requires a graded and comprehensive interpretation. <h3>Objective</h3> We aimed to classify AI severity in patients who underwent endocrine stress tests and analyze their clinical characteristics using real-world medical data. <h3>Design/Setting</h3> This cross-sectional study was conducted at Tokyo Rosai Hospital. <h3>Patients or Other Participants</h3> Inpatients who underwent endocrine stress tests, including the insulin tolerance test, corticotropin-releasing hormone stimulation test (CRHST), and standard-dose and low-dose corticotropin stimulation tests. <h3>Interventions/ Main Outcome Measures</h3> Patients were classified into three groups based on hormone responses: overt AI, suspected early-stage AI, and normal adrenal function. Clinical characteristics, laboratory findings, and treatment interventions were analyzed across groups. <h3>Results</h3> The 104 patients (mean age 46.4±13.5 years, 18.9% male, body mass index 24.3±6.7) exhibited low cortisol levels and fatigue. Among 90 patients completing severity-classifying tests, 19 (21.1%) had overt AI, 38 (42.2%) had suspected early-stage AI, and 33 (36.7%) had normal adrenal function. CRHST results indicated varying pituitary-adrenal axis function based on AI severity. <h3>Conclusions</h3> In routine care, a pragmatic classification combining stress tests can help stratify suspected cases. These findings underscore the importance of flexible and comprehensive interpretation of dynamic endocrine stress tests to detect diverse and subtle dysfunctions of the hypothalamic-pituitary-adrenal axis.